Despite increasingly sophisticated critical care, the mortality of septic shock remains elevated. Accordingly, care remains supportive. Volume resuscitation combined with vasopressor support remains ...the standard of care as adjuvant therapy, and many consider dopamine to be the pressor of choice. Because of fear of excessive vasoconstriction, norepinephrine is considered to be deleterious. The present study was designed to identify factors associated with outcome in a cohort of septic shock patients. Special attention was paid to hemodynamic management and to the choice of vasopressor used, to determine whether the use of norepinephrine was associated with increased mortality.
Prospective, observational, cohort study.
Intensive care unit of a university hospital.
Ninety-seven adult patients with septic shock.
Data from these patients were examined to select variables independently and significantly associated with outcome during the hospital stay. Nineteen clinical, biological, and hemodynamic variables were collected at study entry or during the first 48-72 hrs and analyzed for each patient. A stepwise logistic regression analysis and a model building strategy were used to identify variables independently and significantly associated with outcome. The overall hospital mortality was 73% (71 patients). Five variables were significantly associated with outcome. One factor was strongly associated with a favorable outcome: the use of norepinephrine as part of the hemodynamic support of the patients. The 57 patients who were treated with norepinephrine had significantly lower hospital mortality (62% vs. 82%, p < .001; relative risk = 0.68; 95% confidence interval = 0.54-0.87) than the 40 patients treated with vasopressors other than norepinephrine (high-dose dopamine and/or epinephrine). Four variables were associated with a poor outcome and significantly higher hospital mortality: pneumonia as a cause of septic shock (82% vs. 61%, p < .03; relative risk = 1.47; 95% confidence interval = 1.07-1.77), organ system failure index < or = 3 (92% vs. 60%, p < .001; relative risk = 1.47; 95% confidence interval = 1.17-1.82), low urine output at entry to the study (88% vs. 60%, p < .01; relative risk = 1.44; 95% confidence interval = 1.06-1.87), and admission blood lactate concentration > 4 mmol/L (91% vs. 63%, p < .01; relative risk = 1.60; 95% confidence interval = 1.27-1.84).
Our results indicate that the use of norepinephrine as part of hemodynamic management may influence outcome favorably in septic shock patients. The data contradict the notion that norepinephrine potentiates end-organ hypoperfusion, thereby contributing to increased mortality. However, the present study suffers from some limitation because of its nonrandomized, open-label, observational design. Hence, a randomized clinical trial is needed to clearly establish that norepinephrine improves mortality of patients with septic shock, as compared with high-dose dopamine or epinephrine. Pneumonia as the cause of septic shock, high blood lactate concentration, and low urine output on admission are strong indicators of a poor prognosis. Multiple organ failure is confirmed as a reliable predictor of mortality in septic patients.
Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy, affecting 1 in 2,500 people. The only treatment currently available is rehabilitation or corrective surgery. The ...most frequent form of the disease, CMT-1A, involves abnormal myelination of the peripheral nerves. Here we used a mouse model of CMT-1A to test the ability of ascorbic acid, a known promoter of myelination, to correct the CMT-1A phenotype. Ascorbic acid treatment resulted in substantial amelioration of the CMT-1A phenotype, and reduced the expression of PMP22 to a level below what is necessary to induce the disease phenotype. As ascorbic acid has already been approved by the FDA for other clinical indications, it offers an immediate therapeutic possibility for patients with the disease.
The impact of a contributive result of open-lung biopsy on the outcome of patients with acute respiratory distress syndrome (ARDS) has not been extensively investigated. The aim of this study was ...therefore to determine the rate of contributive open-lung biopsy and whether it improved the prognosis of ARDS patients.
Prospective study conducted during an 8-yr period.
A 14-bed medico-surgical intensive care unit and a 12-bed medical intensive care unit from the same hospital.
One hundred open-lung biopsies were performed in 100 patients presenting ARDS.
Open-lung biopsy was performed after > or = 5 days of evolution of ARDS when there was no improvement in the respiratory status despite negative microbiological samples cultures and potential indication for corticosteroid treatment.
Ten patients presented a mechanical complication following open-lung biopsy (two pneumothoraces and eight moderate air leaks). The unique independent factor associated with this complication was the minute ventilation when open-lung biopsy was performed (odds ratio, 1.20; 95% confidence interval, 1.03-1.41; p = .02). Fibrosis was noted in 53 patients but was associated with an infection in 29 of these 53 patients (55%). A contributive result of open-lung biopsy (defined as the addition of a new drug) was noted in 78 patients. Simplified Acute Physiology Score II was the only independent predictive factor of a contributive open-lung biopsy (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; p = .04). Survival was higher in patients with a contributive open-lung biopsy (67%) than in patients in whom open-lung biopsy results did not modify the treatment (14%) (p < .001). The factors predicting survival were a contributive result of open-lung biopsy, female gender, and the Organ System Failures score the day of open-lung biopsy.
The present study shows that open-lung biopsy provided a contributive result in 78% of ARDS patients with a negative bronchoalveolar lavage. Survival of ARDS patients improved when open-lung biopsy was contributive.
Recent observations suggest the existence of clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all clonazepam data of several epidemiological tools ...of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. In OSIAP survey, the proportion of clonazepam falsified prescriptions among all BZD falsified prescriptions increased. During the 2006 OPPIDUM survey, the analysis of the BZD modalities of use highlights clonazepam abuse liability (for example 23% of illegal acquisition), in second rank after flunitrazepam. Studies based on data from the French health reimbursed system show that 1.5% of subjects with clonazepam dispensing had a deviant behaviour. Among BZD, clonazepam has the second most important doctor‐shopping indicator (3%) after flunitrazepam. All these data provide some arguments in favour of clonazepam abuse liability in real life and the necessity to reinforce its monitoring.
Abstract Background Two methods have been recently developed from a drug reimbursement database to provide useful indicators for public health authorities concerning the abuse potential of ...psychotropic drugs. The doctor-shopping indicator (DSI) measures the proportion of the drug obtained by doctor shopping among the overall quantity of the drug reimbursed and the clustering method reveals subgroups of deviant patients. Objective The objective of the study was to analyze and compare indicators resulting from these two methods, applied to High Dosage Buprenorphine (HDB) (a product well-known to be diverted in France), in order to determine which public health authorities needs they answer. Data analysis The patients with reimbursed HDB were grouped using the clustering method in terms of drug dispensations characteristics over a nine month period. The characteristics of the resulting subgroups, including their DSI, were then compared. Results 4787 Patients (73.4%) had no measurable doctor-shopping behaviour. But the comparison of the two methods demonstrated that the more a patient's profile was characterized by deviant behavior, the higher was the DSI: from 0.4% in a subgroup with a median profile to 72% in a subgroup with a deviant profile. Conclusion These two methods are useful surveillance tools for public health authorities: the clustering method may help devise pertinent intervention strategies to reduce prescription drug abuse while the DSI method provides quantitative information demonstrating whether these strategies are useful. We discuss the advantages and disadvantages of using these two methods as useful indicators for public health authorities.
To assess the influence of the timing of nephrology referral on the short- and long-term outcome of hemodialysis patients, we retrospectively studied 309 patients who had end-stage renal failure and ...entered the chronic hemodialysis program in Sainte-Marguerite University Hospital between January 1, 1989, and December 31, 1996. We excluded from the analysis five patients without available data on referral pattern and 34 patients with irreversible acute renal failure. Of the remaining 270 patients, 177 patients (58%) had an early referral (ER) 16 or more weeks before the start of dialysis, and 93 patients (31%) had a late referral (LR) of less than 16 weeks before dialysis. Short-time morbidity (initial emergent dialysis, pulmonary edema, severe hypertension, temporary vascular access placement for first dialysis, prolonged initial hospitalization) was significantly more frequent in LR patients. Long-term evolution (mean follow-up, 26.5 ± 26 months) did not differ between the two groups. The number of days of hospitalization per patient-year at risk beyond the third month was 21.5 ± 33.7 days for ER and 21.1 ± 36 days for LR patients. Survival analysis showed no difference between the two groups: 3-month survival rates were 96% in both groups, 1-year survival rates were 90% in the ER and 89% in the LR group, and 5-year survival rates were 52% in the ER and 56% in the LR group. In a Cox hazards regression model, referral pattern was not associated with a greater risk for death. In conclusion, delayed nephrology referral generated strikingly greater initial morbidity, but long-term outcome of hemodialysis patients was not modified by delayed nephrological care.
Fourteen benzodiazepine (BZD) or BZD-like medications were analyzed with three data sources aiming to assess prescription drug abuse for the year 2008. After a descriptive analysis, a principal ...component analysis was carried out to explore correlations between seven indicators obtained by different methods using these three different data sources and to compute a composite score of diversion for these drugs. For all the indicators, flunitrazepam appears first with much higher values than the other drugs, whereas clonazepam appears in the second or third place. These methods produce globally correlated indicators and the composite score obtained from principal component analysis ranks the drugs with the highest diversion as follows: flunitrazepam, clonazepam, oxazepam, diazepam, and bromazepam. This study shows that these methods yield consistent results. Their integration into a single multi-indicator approach gives health authorities a global view of different behaviors regarding diversion of a given drug.
To evaluate long-term survival and functional outcome in intensive care unit survivors after mechanical ventilation for intracerebral hemorrhage.
Retrospective chart review and prospective follow-up ...study.
Outpatient follow-up.
Between 1997 and 2000, 120 patients were mechanically ventilated for an intracerebral hemorrhage at our intensive care unit. Sixty-two patients were discharged from hospital (in-hospital mortality = 48%). Sixty patients were evaluated for survival and functional outcome (two were lost to follow-up). Time between discharge and follow-up was > or =1 yr and was a mean of 27 +/- 14 months (range, 12-56).
None.
Patients' physicians were first asked about survival, and patients or proxies were interviewed by phone. Barthel Index and modified Rankin Scale scores were collected, and demographic information and general data were reviewed. The estimated life-table survival curve after discharge was 64.6% at 1 yr and 57% at 3 yrs. In the 24 patients who died, the mean time between discharge and death was 5 +/- 6 months. Probability of death after discharge significantly increased if age at admission was >65 yrs (p <.01; odds ratio, 3.5; 95% confidence interval, 1.4-9.1) and if Glasgow Coma Scale score at discharge was <15 (p <.01; odds ratio, 3.9; 95% confidence interval, 1.6-9.5). In the 36 long-term survivors, Barthel Index was 67.5 +/- 15 (median +/- median absolute dispersion) and modified Rankin Scale score was 2.6 +/- 0.5. Fifteen patients (42%) had a slight or no disability (Barthel Index > or =90 and modified Rankin Scale score < or =2), whereas 21 patients (58%) had moderate or severe disability (Barthel Index < or =85 and modified Rankin Scale score >2).
Probability of survival at 3 yrs after mechanical ventilation for an intracerebral hemorrhage was >50%. Age was an important determinant of long-term survival. Forty-two percent of long-term survivors were independent for activities of daily living. Only a few long-term survivors had a very high degree of disability.
